NAN, A NOVEL VOLTAGE-GATED NA CHANNEL, IS EXPRESSED PREFERENTIALLY INPERIPHERAL SENSORY NEURONS AND DOWN-REGULATED AFTER AXOTOMY

Although physiological and pharmacological evidence suggests the prese nce of multiple tetrodotoxin-resistant (TTS-R) Na channels in neurons of peripheral nervous system ganglia, only one, SNS/PN3, has been iden tified in these cells to date. we have identified and sequenced a nove l Na channel cu-subunit (NaN), predicted to be TTX-R and voltage-gated , that is expressed preferentially in sensory neurons within dorsal ro ot ganglia (DRG) and trigeminal ganglia, The predicted amino acid sequ ence of NaN can be aligned with the predicted structure of known Na ch annel alpha-subunits; all relevant landmark sequences, including posit ively charged S4 and pore-lining SS1-SS2 segments, and the inactivatio n tripeptide IFM, are present at predicted positions. However, NaN exh ibits only 42-53% similarity to other mammalian Na channels, including SNS/PN3, indicating that it is a novel channel, and suggesting that i t mag represent a third subfamily of Na channels. NaN transcript level s are reduced significantly 7 days post axotomy in DRG neurons, consis tent with previous findings of a reduction in TTX-R Na currents. The p referential expression of NaN in DRG and trigeminal ganglia and the re duction of NaN mRNA levels in DRG after axonal injury suggest that NaN , together with SNS/PN3, may produce TTX-R currents in peripheral sens ory neurons and may influence the generation of electrical activity in these cells.